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Sputum Eosinophils and the Response of Exercise-Induced Bronchoconstriction to Corticosteroid in Asthma^*

^* From the Department of Medicine (Drs. Duong, Inman, and O’Byrne, Mr. Obminski, and Ms. Strinich), McMaster University, Hamilton, ON, Canada; Hospital for Sick Children (Dr. Subbarao), University of Toronto, Toronto, ON, Canada; Umea University (Dr. Adelroth), Umea, Sweden; and the University of Southern Denmark (Dr. Pedersen), Kolding, Denmark.

Correspondence to: MyLinh Duong, MBBS, McMaster University, 1200 Main St West, Room 3U-24, Hamilton, ON, Canada L8N 3Z5; e-mail: duongmy{at}mcmaster.ca

Abstract

Background: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined.

Methods: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 µg daily; and (2) 80 vs 320 µg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed.

Results: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia 5%. Only high-dose ICS therapy (ie, 160 and 320 µg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 µg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time.

Conclusions: These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs.

Trial registration: clinicaltrial.gov; Identifier: NCT00525772 [ClinicalTrials.gov]

Key Words: exercise-induced bronchoconstriction • inhaled corticosteroids • sputum eosinophils • steroid responsiveness